The Ca2+ release-activated Ca2+ (CRAC) channel is an essential ion channel in the store operated Ca2+ (SOC) channel family. The CRAC channel is comprised of a complex of plasma membrane-resident Orai and endoplasmic reticulum-resident stromal interaction molecule (STIM) proteins. Orai1, Orai2, and Orai3 are members of the Orai family of proteins. Orai1 is expressed on the plasma membrane and is the principle Ca2+-selective pore-forming channel subunit in human leukocytes. Orai signaling is implicated in, for example, cancer, immunological diseases, and neurological diseases.